P1600: USE OF RITUXIMAB PLUS STANDARD OF CARE FOR TREATMENT OF PRIMARY IMMUNE THROMBOCYTOPENIA: A SYSTEMATIC REVIEW AND META-ANALYSIS
Authors: Ali Eshaghpour, Philip Yu, Sarah Ge, Roger Kou, Nathalie Loeb, Mark Crowther
Journal: HemaSphere (2023)

Topic: 32. Platelet disorders Background: Immune thrombocytopenia (ITP) is a common autoimmune disease associated with decreased platelet counts and increased risk of bleeding. The exact pathophysiology of ITP is still poorly understood, with multiple immune mediated pathways being theorized to contribute. Treatment of this condition is done with the goal of sustained recovery of platelet counts and prevention or cessation of bleeding. If treatment is deemed necessary, first line treatment consists of high dose corticosteroids or intravenous immunoglobulin. Unfortunately for many patients, these treatments produce rapid but transient effects. Rituximab, a monoclonal anti-CD20 antibody, has been shown to improve platelet count response, but evidence for sustained response beyond 6 months is limited. Aims: The objective of this systematic review and meta-analysis is to establish the effect of rituximab on short-term and sustained platelet response in adults with primary ITP. Methods: A comprehensive search of MEDLINE, Embase, and the grey literature was done from inception to September 2022. Studies were screened at abstract and full-text level independently and in duplicate. All English language randomized controlled studies investigating the use of rituximab in addition to standard of care as compared to standard of care were included. Baseline trial characteristics, rituximab dosing regimen, standard of care regimen, and follow up time were collected. Efficacy outcome measures were short-term partial and complete response, and long-term partial and complete response. Partial and complete response were defined by primary study. Short-term was defined as <3 months, whereas long term was defined as >6 months. If multiple time points were presented, longest follow up time was used in analysis. Safety outcomes included bleeding and infection as defined by primary study. Meta-analysis was done using DerSimonioan and Laird random effects model and reported as relative risks (RR) with 95% confidence intervals (CI) Results: Of the 3693 studies screened, five studies with a total of 463 unique patients were included in the analysis. Four trials used standard dosing of rituximab (375 mg/m2), while one trial used low dose rituximab (100 mg). Standard of care in each trial consisted of corticosteroids +- IVIG. Median short-term follow up was 28 days (Range 10 days, 1 month). Median long-term follow up was 12 months (range 6 months, 18 months). Complete response was defined as platelet count >100*109 platelets/L in all studies. Partial response definition varied between >30-50*109 platelets/L. Rituximab is associated with increased short-term partial response (RR 1.34, 95%CI 1.01, 1.77, I2= 68%, N=3), long-term complete response (RR 1.71, 95%CI 1.11, 2.64, I2= 48%, N=4), and long-term partial response (RR 1.58, 95%CI 1.02, 2.44, I2= 74%, N=5). There was insufficient data to analyze short-term complete response. There was no difference between rituximab and standard of care with regards to bleeding (RR 1.06, 95%CI 0.52, 2.13, I2= 3%, N=4). There was a trend towards more infections with rituximab as compared to standard of care (RR 1.41, 95%CI 0.94, 2.14, I2= 0%, N=4). Summary/Conclusion The addition of rituximab may increase both short-term and long-term platelet response rate, with no difference with regards to bleeding as compared to standard of care. There is a trend towards increased infection as compared to standard of care. Evidence regarding sustained response beyond 12 months is limited in this study. Further research including more primary data regarding long-term response and pooled analyses of long-term response are required. Keywords: Immune thrombocytopenia (ITP), Rituximab